Overview
Opioid Toxicity
Quick Reference
Critical Alerts
- Airway is priority: Bag-valve-mask before and while giving naloxone
- Naloxone is the antidote: Give immediately if opioid overdose suspected
- Start with lower doses: Titrate to respiratory drive, not full consciousness
- Fentanyl may require higher/repeated doses of naloxone: More potent opioid
- Observe after naloxone: Opioid may outlast naloxone (renarcotization)
- Consider coingestants: Benzos, alcohol, stimulants, polysubstance use
Key Diagnostics
| Finding | Classic Presentation |
|---|---|
| Mental status | Decreased (drowsy to comatose) |
| Pupils | Pinpoint (miosis) |
| Respiratory rate | Decreased (<12/min), apnea, shallow |
| Skin | Cyanosis if hypoxic |
| Oxygen saturation | Low |
Emergency Treatments
| Intervention | Details |
|---|---|
| Airway support | BVM, O2, suction; intubate if needed |
| Naloxone (intranasal) | 4 mg IN (2 mg per nostril) |
| Naloxone (IV/IM) | 0.04-0.4 mg IV; titrate up to 2-10 mg if needed |
| Repeat naloxone | Every 2-3 minutes if no response |
| Observation | 4-6 hours minimum (longer for long-acting opioids) |
Definition
Overview
Opioid toxicity (opioid overdose) is a potentially fatal condition caused by excessive opioid effect on the central nervous system and respiratory centers, leading to respiratory depression, apnea, and death. It has become a public health crisis due to the opioid epidemic. Rapid recognition and administration of naloxone (Narcan) saves lives.
Opioid Classification
By Potency/Duration:
| Category | Examples | Considerations |
|---|---|---|
| Short-acting | Heroin, morphine, oxycodone IR | 4-6 hour duration |
| Long-acting | Methadone, fentanyl patch, extended-release formulations | Prolonged observation |
| Ultra-potent | Fentanyl (illicit), carfentanil | Higher naloxone doses may be needed |
| Partial agonist | Buprenorphine | Lower overdose risk; harder to reverse |
Common Opioids:
| Name | Notes |
|---|---|
| Heroin | Street drug; often contaminated with fentanyl |
| Fentanyl (illicit) | Extremely potent; major cause of overdose deaths |
| Morphine | Standard opioid |
| Oxycodone | Prescription opioid |
| Hydrocodone | Prescription opioid |
| Methadone | Long-acting; prolonged observation needed |
| Buprenorphine | Partial agonist; ceiling effect |
| Tramadol | Weak opioid; seizure risk |
Epidemiology
- US overdose deaths: >80,000/year (opioid-related)
- Fentanyl now predominates: Most overdose deaths involve synthetic opioids
- Risk groups: IVDU, chronic pain patients, polysubstance users
- Increasing: Deaths continue to rise despite harm reduction efforts
Etiology
Risk Factors for Opioid Overdose:
| Factor | Mechanism |
|---|---|
| Illicit fentanyl contamination | Unintentional high potency |
| Tolerance loss (post-detox/incarceration) | Return to previous dose after abstinence |
| Combining with sedatives (benzos, alcohol) | Additive respiratory depression |
| Prescription opioid misuse | Taking higher doses |
| Opioid-naïve patients | No tolerance |
| Respiratory comorbidities (COPD, sleep apnea) | Reduced respiratory reserve |
Pathophysiology
Mechanism of Opioid Toxicity
- Opioid binds to mu receptors: In brainstem respiratory centers
- Respiratory depression: Decreased respiratory drive, rate, and depth
- Hypoxia: Leads to loss of consciousness
- Apnea and death: If untreated
Other Effects
| System | Effect |
|---|---|
| CNS | Sedation, euphoria, miosis, coma |
| Respiratory | Hypoventilation, apnea |
| Cardiovascular | Hypotension (mild), bradycardia |
| GI | Decreased motility, nausea |
| Skin | Flushing, pruritus |
| Urinary | Retention |
Miosis (Pinpoint Pupils)
- Opioid effect on parasympathetic nucleus
- May be absent with:
- Meperidine (Demerol)
- Coingestants (antihistamines, sympathomimetics)
- Hypoxic brain injury
Clinical Presentation
Classic Toxidrome ("Opioid Triad")
| Feature | Finding |
|---|---|
| Mental Status | Depressed (drowsy, unresponsive) |
| Pupils | Pinpoint (miosis) |
| Respirations | Slow, shallow, apnea |
Other Findings
History (Often Limited)
Key Information (From EMS, bystanders, patient if responsive):
Hypoxia (SpO2 low)
Common presentation.
Cyanosis
Common presentation.
Bradycardia
Common presentation.
Hypotension (usually mild)
Common presentation.
Decreased bowel sounds
Common presentation.
Cool, clammy skin (in overdose)
Common presentation.
Pulmonary edema (NCPE—non-cardiogenic)
Common presentation.
Needle marks (IVDU)
Common presentation.
Red Flags
Life-Threatening Features
| Finding | Concern | Action |
|---|---|---|
| Apnea or agonal breathing | Imminent death | BVM + Naloxone immediately |
| Cyanosis | Severe hypoxia | Ventilate, give O2 |
| Unresponsive | Severe overdose | Full resuscitation |
| Cardiac arrest | Hypoxic arrest | CPR + Naloxone + ACLS |
| Pulmonary edema | NCPE from overdose | Ventilatory support, may improve with naloxone |
| No response to naloxone | Polysubstance, CNS injury, wrong diagnosis | Consider other causes |
Complications
- Aspiration pneumonia
- Rhabdomyolysis (prolonged down time)
- Hypoxic brain injury
- Compartment syndrome
- Death
Differential Diagnosis
Other Causes of Depressed Consciousness with Respiratory Depression
| Diagnosis | Features |
|---|---|
| Benzodiazepine overdose | Flumazenil responsive; but mixed use common |
| Ethanol intoxication | Alcohol on breath, no miosis |
| GHB/Sedative hypnotics | Similar presentation |
| Hypoglycemia | Check glucose; reverses with dextrose |
| Stroke | Focal deficits, may have pupil changes |
| Head trauma | Mechanism, focal findings |
| Sepsis | Fever, infection source |
| Hypothermia | Low temp, exposure history |
| Carbon monoxide poisoning | Exposure history, normal or dilated pupils |
Polysubstance Use
- Extremely common (heroin + fentanyl, opioids + benzos)
- May have mixed toxidromes
- May require multiple antidotes or supportive care
Diagnostic Approach
Clinical Diagnosis
- Opioid overdose is a clinical diagnosis
- Classic triad: Depressed mental status + miosis + respiratory depression
- Response to naloxone is diagnostic
Bedside Assessment
| Test | Purpose |
|---|---|
| Pulse oximetry | Assess hypoxia |
| Fingerstick glucose | Rule out hypoglycemia |
| Temperature | Hypothermia or fever |
| ECG | Arrhythmia, QT prolongation (methadone) |
Laboratory Studies (Not Urgent for Management)
| Test | Purpose |
|---|---|
| ABG/VBG | Hypercapnia, acidosis |
| BMP | Electrolytes, renal function (rhabdomyolysis) |
| Urine drug screen | Confirms opioid (may miss fentanyl) |
| CK | Rhabdomyolysis if prolonged down time |
| Lactate | Perfusion status |
| Acetaminophen, salicylate | Rule out polysubstance |
| Ethanol level | Coingestant |
Urine Drug Screen Limitations
- Many synthetic opioids (fentanyl) are NOT detected on standard screens
- False negatives common
- Do NOT rely on urine drug screen to rule out opioid overdose
- Treat clinically
Treatment
Principles of Management
- Airway and breathing first: Ventilate before/while giving naloxone
- Naloxone for opioid reversal: Titrate to respiratory drive
- Supportive care: IV access, monitoring, address complications
- Observe for renarcotization: Opioid may outlast naloxone
- Address polysubstance use: Other toxins may be present
Airway Management
Before/During Naloxone:
- Open airway (head tilt-chin lift, jaw thrust)
- Suction if needed
- Bag-valve-mask ventilation with high-flow O2
- 100% FiO2 or room air if BVM not available
Intubation Indications:
- Persistent apnea despite naloxone
- Unable to protect airway
- Profound aspiration
- Refractory hypoxemia
Naloxone (Narcan)
Mechanism: Competitive antagonist at mu opioid receptors
Routes and Dosing:
| Route | Dose | Notes |
|---|---|---|
| Intranasal | 4 mg (2 mg per nostril) | Easiest prehospital |
| Intramuscular | 0.4-2 mg | If no IV |
| Intravenous | 0.04-0.4 mg initial | Titrate up; start low in opioid-dependent patient |
| Subcutaneous | 0.4-2 mg | Alternative |
| Endotracheal | 2-4 mg (diluted) | If no IV/IM/IN access |
Titration Strategy:
- Start low (0.04-0.1 mg IV) in opioid-dependent patients to avoid precipitating withdrawal
- Goal: Restore respiratory drive, NOT full consciousness
- May repeat every 2-3 minutes up to 10 mg total
- If no response after 10 mg: Reconsider diagnosis
Fentanyl Overdose:
- May require higher and repeated doses (some case reports of >10 mg needed)
- Maintain ventilation while titrating
Duration of Action:
- Naloxone: 30-90 minutes
- Many opioids (heroin, long-acting formulations, methadone): Much longer
- Risk of renarcotization when naloxone wears off
Observation Period
| Opioid Type | Observation Duration |
|---|---|
| Short-acting (heroin, morphine IR) | 4-6 hours |
| Long-acting (methadone, extended-release) | 12-24 hours |
| Fentanyl patch | Prolonged (patch may still be releasing) |
| Buprenorphine | Shorter observation (ceiling effect) |
Naloxone Infusion (If Repeated Reversal Needed)
Indication: Recurrent respiratory depression despite boluses
Preparation:
- Infuse 2/3 of the effective bolus dose per hour
- Example: If 0.4 mg reversed symptoms, infuse ~0.25 mg/hour
Withdrawal Symptoms (After Naloxone)
| Symptoms | Management |
|---|---|
| Agitation, anxiety | Reassurance, benzodiazepines if severe |
| Vomiting, diarrhea | Antiemetics, fluids |
| Diaphoresis, tachycardia | Supportive |
| Pain | Non-opioid analgesia if possible |
Supportive Care
| Intervention | Details |
|---|---|
| IV fluids | For hypotension, rhabdomyolysis |
| Monitor glucose | Correct hypoglycemia |
| ECG | QT prolongation (methadone); arrhythmias |
| Warming | If hypothermic |
| CK monitoring | If prolonged down time |
| Chest X-ray | Aspiration, non-cardiogenic pulmonary edema |
Disposition
Discharge Criteria
- Observed minimum 4-6 hours (longer for long-acting opioids)
- No recurrent respiratory depression after naloxone wearing off
- Stable mental status
- No complications (aspiration, rhabdomyolysis)
- Able to tolerate oral intake
- Safe discharge plan (not alone, follow-up, naloxone kit)
Admission Criteria
- Long-acting opioid ingestion (methadone, ER oxycodone)
- Repeated naloxone doses required
- Naloxone infusion required
- Respiratory complications (aspiration, pulmonary edema)
- Rhabdomyolysis
- Altered mental status not fully resolved
- Unknown coingestants
ICU Admission
- Intubated patient
- Persistent hemodynamic instability
- Severe complications
Leaving Against Medical Advice (AMA)
- Document mental capacity if alert and oriented
- Provide naloxone kit if available
- Harm reduction counseling
- Provide information on OUD treatment
Follow-Up and Harm Reduction
- Offer treatment for opioid use disorder (buprenorphine, methadone)
- Prescribe naloxone kit (Narcan) for patient and family
- Provide overdose prevention education
- Connect with addiction services/SAMHSA
Patient Education
Condition Explanation (For Patient and Family)
- "You had an opioid overdose, which means the drug slowed your breathing and made you unconscious."
- "Naloxone (Narcan) reversed the overdose."
- "You are at risk of this happening again."
- "Narcan saves lives—keep it available and teach others how to use it."
Overdose Prevention
- Never use alone
- Start with small dose after tolerance break
- Avoid mixing opioids with benzos/alcohol
- Test substances (fentanyl test strips)
- Carry naloxone and teach others to use it
Recognizing Overdose (Teach Bystanders)
- Unresponsive, unable to wake
- Slow or stopped breathing
- Choking or gurgling sounds
- Blue lips/fingertips
What to Do (Teach Bystanders)
- Call 911
- Give naloxone (nasal spray or injection)
- Perform rescue breathing
- Place in recovery position
- Stay with person until help arrives
Special Populations
Opioid-Dependent Patients
- Lower starting dose of naloxone (0.04-0.1 mg IV)
- Titrate to respiratory drive, not arousal
- Precipitating severe withdrawal can cause:
- Agitation, combativeness
- Vomiting → aspiration risk
- Seizures (rare)
- Patient leaving AMA
Pregnancy
- Naloxone is safe and should be given
- May precipitate withdrawal in fetus
- OB consultation
- Neonatal abstinence syndrome may occur
Pediatric
- Opioid exposure (accidental ingestion)
- Naloxone dosing: 0.1 mg/kg IV/IM/IN (max 2 mg)
- Repeat as needed
Cardiac Arrest Secondary to Opioid Overdose
- Standard ACLS plus naloxone 2 mg IV/IO (or IM/IN if no access)
- Airway and ventilation are critical
- CPR as per guidelines
Quality Metrics
Performance Indicators
| Metric | Target | Rationale |
|---|---|---|
| Naloxone given for suspected opioid OD | 100% | Life-saving |
| Observation > hours post-reversal | 100% | Prevent renarcotization |
| Naloxone kit prescribed at discharge | >0% | Harm reduction |
| OUD treatment offered/referred | 100% | Reduce future overdoses |
| Education provided to patient/family | 100% | Prevention |
Documentation Requirements
- Suspected substances
- Time of ingestion/injection (if known)
- Prehospital naloxone dose and response
- Hospital naloxone dose and response
- Observation period and stability
- Discharge plan and harm reduction
Key Clinical Pearls
Diagnostic Pearls
- Classic triad: CNS depression + miosis + respiratory depression
- Miosis may be absent: Meperidine, mixed ingestions, hypoxic injury
- Urine drug screens miss fentanyl: Treat clinically, not based on screen
- Polysubstance use is common: May not fully reverse with naloxone alone
- Response to naloxone = diagnostic and therapeutic
Treatment Pearls
- Ventilate while you're giving naloxone: BVM before and during
- Start low in opioid-dependent patients: Avoid severe withdrawal
- Titrate to respiratory drive, not consciousness: Keep breathing, stay calm
- Fentanyl may require high/repeated doses: Keep giving and keep ventilating
- Renarcotization risk: Observe 4-6 hours minimum (longer for long-acting)
- Never withholdMicrosoftInternetExplorer4 naloxone for fear of withdrawal: Respiratory arrest is worse
Disposition Pearls
- Must observe after naloxone: Opioid often outlasts naloxone
- Prescribe take-home naloxone: All overdose patients
- Offer OUD treatment: ED-initiated buprenorphine saves lives
- Connect to services: Social work, addiction medicine, harm reduction
References
- Boyer EW. Management of Opioid Analgesic Overdose. N Engl J Med. 2012;367(2):146-155.
- Schiller EY, et al. Opioid Overdose. StatPearls. 2024.
- Chou R, et al. Management of Suspected Opioid Overdose With Naloxone in Out-of-Hospital Settings: A Systematic Review. Ann Intern Med. 2017;167(12):867-875.
- CDC. Opioid Overdose Prevention. https://www.cdc.gov/opioids/overdose-prevention/index.html. 2024.
- SAMHSA. Opioid Overdose Prevention Toolkit. 2018.
- Yealy DM, et al. Opioid overdose. N Engl J Med. 2021;384(22):2136-2144.
- van Dorp EL, et al. Naloxone in opioid poisoning: clinical pharmacology and recommendations for use. Br J Clin Pharmacol. 2018;84(6):1172-1181.
- UpToDate. Acute opioid intoxication in adults: Clinical features and course. 2024.